肿瘤细胞治疗研究
英文原题：Synergizing immunity: lipid nanoparticle-mediated mRNA and gene delivery as a next-gen paradigm in cancer immunotherapy.
这些见解强调了LNP作为下一代mRNA癌症免疫疗法的变革性载体，并指出了克服递送和免疫微环境障碍的未来方向。
基于信使 RNA（mRNA）的治疗药物通过实现肿瘤抗原、细胞因子和免疫调节剂的瞬时、非整合性表达，彻底改变了癌症免疫治疗。然而，mRNA 固有的不稳定性和免疫原性需要以脂质纳米颗粒（LNP）为代表的高效递送平台。本综述全面讨论了 LNP 在癌症免疫治疗中用于 mRNA 和基因递送的演变、设计和应用。我们探讨了其理化性质、细胞摄取机制、内体逃逸和免疫原性潜力，以及用于肿瘤靶向的表面工程策略。特别强调了基于 LNP 的 mRNA 疫苗、CAR-T 细胞工程、双特异性抗体递送和联合疗法的最新进展。本文综合了临床前研究、临床试验和可扩展制造创新（包括微流控和切向流过滤）的见解。此外，我们还讨论了影响临床转化的储存稳定性、免疫毒性和监管障碍。总之，这些见解强调了 LNP 作为下一代 mRNA 癌症免疫治疗的变革性载体，并突出了克服递送和免疫微环境障碍的未来方向。
Messenger RNA (mRNA)-based therapeutics have revolutionised cancer immunotherapy by enabling transient, non-integrating expression of tumour antigens, cytokines, and immunomodulators. However, the inherent instability and immunogenicity of mRNA necessitate efficient delivery platforms led by lipid nanoparticles (LNPs). This review comprehensively discusses the evolution, design, and application of LNPs for mRNA and gene delivery in cancer immunotherapy. We explore their physicochemical properties, mechanisms of cellular uptake, endosomal escape, and immunogenic potential, alongside surface engineering strategies for tumour targeting. Special emphasis is placed on recent advances in LNP-based mRNA vaccines, CAR-T cell engineering, bispecific antibody delivery, and combinatorial therapies. The article synthesizes insights from preclinical studies, clinical trials, and scalable manufacturing innovations, including microfluidics and tangential flow filtration. Furthermore, we address storage stability, immunotoxicity, and regulatory hurdles that shape clinical translation. Together, these insights underscore LNPs as a transformative vehicle for next-generation mRNA cancer immunotherapies and highlight future directions in overcoming delivery and immune landscape barriers.
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